Aptamer Targets Triple-Negative Breast Cancer through Specific Binding to Surface CD49c
Although targeted cancer therapy can induce higher therapeutic efficacy and cause fewer side effects in patients, the lack of targetable biomarkers on triple-negative breast cancer (TNBC) cells limits the development of targeted therapies by antibody technology. Therefore, we investigated an alterna...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/6/1570 |
| _version_ | 1797446896789225472 |
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| author | Quanyuan Wan Zihua Zeng Jianjun Qi Yingxin Zhao Xiaohui Liu Zhenghu Chen Haijun Zhou Youli Zu |
| author_facet | Quanyuan Wan Zihua Zeng Jianjun Qi Yingxin Zhao Xiaohui Liu Zhenghu Chen Haijun Zhou Youli Zu |
| author_sort | Quanyuan Wan |
| collection | DOAJ |
| description | Although targeted cancer therapy can induce higher therapeutic efficacy and cause fewer side effects in patients, the lack of targetable biomarkers on triple-negative breast cancer (TNBC) cells limits the development of targeted therapies by antibody technology. Therefore, we investigated an alternative approach to target TNBC by using the PDGC21T aptamer, which selectively binds to poorly differentiated carcinoma cells and tumor tissues, although the cellular target is still unknown. We found that synthetic aptamer probes specifically bound cultured TNBC cells in vitro and selectively targeted TNBC xenografts in vivo. Subsequently, to identify the target molecule on TNBC cells, we performed aptamer-mediated immunoprecipitation in lysed cell membranes followed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Sequencing analysis revealed a highly conserved peptide sequence consistent with the cell surface protein CD49c (integrin α3). For target validation, we stained cultured TNBC and non-TNBC cells with an aptamer probe or a CD49c antibody and found similar cell staining patterns. Finally, competition cell-binding assays using both aptamer and anti-CD49c antibody revealed that CD49c is the biomarker targeted by the PDGC21T aptamer on TNBC cells. Our findings provide a molecular foundation for the development of targeted TNBC therapy using the PDGC21T aptamer as a targeting ligand. |
| first_indexed | 2024-03-09T13:47:13Z |
| format | Article |
| id | doaj.art-6a9d624be763411fac51e290c8d962ce |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T13:47:13Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-6a9d624be763411fac51e290c8d962ce2023-11-30T20:57:16ZengMDPI AGCancers2072-66942022-03-01146157010.3390/cancers14061570Aptamer Targets Triple-Negative Breast Cancer through Specific Binding to Surface CD49cQuanyuan Wan0Zihua Zeng1Jianjun Qi2Yingxin Zhao3Xiaohui Liu4Zhenghu Chen5Haijun Zhou6Youli Zu7Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX 77030, USADepartment of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX 77030, USADepartment of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX 77030, USADepartment of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX 77030, USADepartment of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX 77030, USADepartment of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX 77030, USADepartment of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX 77030, USAAlthough targeted cancer therapy can induce higher therapeutic efficacy and cause fewer side effects in patients, the lack of targetable biomarkers on triple-negative breast cancer (TNBC) cells limits the development of targeted therapies by antibody technology. Therefore, we investigated an alternative approach to target TNBC by using the PDGC21T aptamer, which selectively binds to poorly differentiated carcinoma cells and tumor tissues, although the cellular target is still unknown. We found that synthetic aptamer probes specifically bound cultured TNBC cells in vitro and selectively targeted TNBC xenografts in vivo. Subsequently, to identify the target molecule on TNBC cells, we performed aptamer-mediated immunoprecipitation in lysed cell membranes followed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Sequencing analysis revealed a highly conserved peptide sequence consistent with the cell surface protein CD49c (integrin α3). For target validation, we stained cultured TNBC and non-TNBC cells with an aptamer probe or a CD49c antibody and found similar cell staining patterns. Finally, competition cell-binding assays using both aptamer and anti-CD49c antibody revealed that CD49c is the biomarker targeted by the PDGC21T aptamer on TNBC cells. Our findings provide a molecular foundation for the development of targeted TNBC therapy using the PDGC21T aptamer as a targeting ligand.https://www.mdpi.com/2072-6694/14/6/1570aptamer ligandbiomarker identificationintegrin α3/CD49ctriple-negative breast cancer (TNBC)targeted cancer therapy |
| spellingShingle | Quanyuan Wan Zihua Zeng Jianjun Qi Yingxin Zhao Xiaohui Liu Zhenghu Chen Haijun Zhou Youli Zu Aptamer Targets Triple-Negative Breast Cancer through Specific Binding to Surface CD49c Cancers aptamer ligand biomarker identification integrin α3/CD49c triple-negative breast cancer (TNBC) targeted cancer therapy |
| title | Aptamer Targets Triple-Negative Breast Cancer through Specific Binding to Surface CD49c |
| title_full | Aptamer Targets Triple-Negative Breast Cancer through Specific Binding to Surface CD49c |
| title_fullStr | Aptamer Targets Triple-Negative Breast Cancer through Specific Binding to Surface CD49c |
| title_full_unstemmed | Aptamer Targets Triple-Negative Breast Cancer through Specific Binding to Surface CD49c |
| title_short | Aptamer Targets Triple-Negative Breast Cancer through Specific Binding to Surface CD49c |
| title_sort | aptamer targets triple negative breast cancer through specific binding to surface cd49c |
| topic | aptamer ligand biomarker identification integrin α3/CD49c triple-negative breast cancer (TNBC) targeted cancer therapy |
| url | https://www.mdpi.com/2072-6694/14/6/1570 |
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